Movement disorders refer to a number of conditions including Hypokinesia (Parkinson's disease), Hyperkinetic disorders (L-dopa induced dyskinesia, Hemiballism and Chorea), Dystonia (generalized and localized) and Tremor (Resting, Postural and Action tremor).
Parkinson's disease (PD) is a chronic, progressive neurodegenerative movement disorder. The main symptoms are tremors, rigidity, slow movement (bradykinesia), poor balance and difficulty walking. The highest prevalence of PD is in Europe and North America with around 1 to 1.5 million people being affected in the USA. Caucasian populations are affected more than others, with a prevalence of around 120-180 per 100,000 people. Symptoms of PD may appear at any age, but the average age of onset is 60. PD is rare in young people and risk increases with age. The cause of the disease is unknown, but there may be genetic factors.
PD is associated with degeneration of several neuronal modulators in the midbrain that primarily affect the motor system. These include the midbrain dopaminergic nuclei, the serotoninergic median raphe nuclei, the noradrenergic locus coeruleus and the cholinergic pedunculopontine nucleus.
At present, there is no cure for PD. Medical treatment for PD relies on a variety of drugs that stimulate dopamine receptors and although this approach may be effective for 5-10 years, therapy is complicated by motor side effects including “on/off” fluctuations and dyskinesias. With progressive degeneration of the dopaminergic system and other neuronal modulators the patient develops fluctuating responses to medical intervention. Surgery may be contemplated in patients who are poorly controlled on the best medical therapy.
Hyperkinetic disorders are sudden rapid involuntary and purposeless movements that typically intrude into the patient's normal activity. These movements may be both axial and peripheral. Examples of hyperkinetic disorders include L-Dopa dyskinesia, which is a complication of PD, Chorea and Hemiballism, which may result from brain lesions involving the basal ganglia. There are no effective medical treatments for these conditions.
Dystonia is a postural disorder characterized by involuntary muscle contractions affecting various parts of the body including the limbs, trunk, shoulders, face and neck.
Tremor is involuntary oscillatory movements produced by alternating contractions of agonist and antagonist muscles. These movements can affect the proximal and distal limb muscles and also the axial muscle groups. Tremor can occur at rest, with the limb maintained in a particular posture and/or during movements. Tremor can occur as a sign of PD, and as a result of lesions of the basal ganglia, midbrain or the cerebellum, but its most common form is familial Essential Tremor (ET). Medical treatments tend to variably suppress rather than abolish tremor.
At present there are various surgical treatments available for movement disorders; however, many of them involve side effects. Movement disorders are due to abnormal patterns of neuronal firing permeating the motor pathways. Surgical treatment aims to disrupt the transmission of these abnormal patterns by destroying or lesioning motor pathways or nuclei or alternatively overriding the abnormal patterns with high frequency electrical stimulation. The latter treatment is known as Deep Brain Stimulation (DBS) and is achieved by implanting an electrode into the pathways or nuclei in the brain and delivering pulsed electrical current to the tissue from an implanted pulse generator which is connected to the electrode.
A number of targets are known to be effective in the treatment of movement disorders. These include the Globus Pallidus Internus (Gpi), the Ventral Intermediate Nucleus (Vim) of the thalamus and the Subthalamic Nucleus (STN).
Lesions or DBS of the Gpi can be effective for the treatment of PD, Dystonia and Hyperkinetic movements. This type of treatment has a modest effect on PD symptoms such as tremor, rigidity, bradykinesia and akinesia, but is effective in treating the motor side effects of L-dopa therapy such as dyskinesia and dystonia which allow the patient to continue on a high dose of medication.
Bilateral Gpi lesions/DBS are associated with worsening axial symptoms including deterioration in speech, swallowing and gait.
The conventional method for placing stimulating or lesioning electrodes in subcortical targets for treating movement disorders involves 3 steps:
1/Identifying the target on radiological images of the patient's brain either directly, or indirectly with reference to a brain atlas.
2/Registering the spatial information on the image to an aiming instrument or stereoguide. This is conventionally done by fixing a frame to the patient's head that carries fiducials that can be visualised on the brain images and from which the stereoguide's Cartesian coordinate system can be determined. The coordinates of the target are then set in the stereoguide that in turn is fixed to the frame.
3/Implanting the electrode and confirming its location peri-operatively. Conventionally electrode placement is carried out through a frontal burr hole with the patient awake. Stimulation of the target site during the procedure confirms appropriate placement by inducing symptomatic improvement. Target localisation can also be confirmed with micro-electrode recording. Here micro-electrodes are passed through the region of interest in the brain until neuronal firing patterns characteristic of the target are recorded. In recent years some groups have been implanting DBS electrodes in anaesthetised patients and confirming accurate electrode placement with peri-operative imaging alone.
The conventional trans-frontal approach to functional neurosurgical targets has the disadvantage that the electrode trajectory (which is approximately 45 degrees to the anterior commissure (AC)—posterior commissure (PC) plane) is generally orthogonal to the elongate functional topography of the basal ganglia. This generally limits the field of stimulation to a small portion of the motor representation of the target nucleus so limiting the potential therapeutic benefit.
The constraints imposed by the established trans-frontal trajectory require the surgeon to select a location in the target nucleus that may best treat the most dominant features of the patient's disease. By way of example, the STN is one of the most frequently targeted structures for the treatment of Parkinson's disease with DB S and its dorso-caudal half is attributed with motor function. A surgeon wishing to treat a PD patient with akinesia as a dominant symptom may target the middle of the STN, at the junction of its motor and associative portions, but if treating a patient with tremor and rigidity then targeting the more posterior portions of the dorso-caudal nucleus would give better symptomatic control. However, patients with PD have variable and progressive symptoms and so it is difficult to target a single location along the rostro-caudal functional topography that will effectively control all symptoms.
Indeed, in addition to motor functions, the STN has limbic and associative functions. Disruption of these with DBS may contribute to worsening anxiety and depression seen with this treatment. Medial to the STN are fibers carrying cerebellar information to the thalamus and spread of current to these may interfere with information regarding precision movements of the larynx and hence cause worsening of speech. Stimulation of structures rostral and ventral to the subthalamic nucleus including the substantia nigra and area of Sano are associated with severe depression and mania/rage respectively.
Although bilateral simulation of the STN is currently regarded as the optimum target by many neurosurgical centers, the most effective therapeutic contact on a quadripolar DBS lead transfixing the STN has been reported as being one positioned at the interface of the dorsal surface of the STN and the adjacent white matter tracts.
Murata et al., describe stimulating the posterior subthalamic area for treating proximal tremor. The surgery utilised a conventional frontal burr hole approach. The treatment area selected by Murata et al. is particularly close to the prelemniscal radiation. Stimulation of this area can result in severe side effects such as speech disturbances, difficulty with precision movements and postural problems.
In view of the problems associated with DBS, there is a need for improved methods for treating movement disorders.